“Simulations of the dynamics at an RNA-protein interface” The paper: “Simulations of the dynamics at an RNA-protein interface” Hermann T. & Westhof E. Nature Structural Biology,volume 6, number 6, June 1999 The protein: Fig1: Tertiary structure of U1A. Beta sheets as yellow arrows and alpha helices coloured red.

The secondary structure elements of U1A and the RNA sequence. Why did the authors do the work? A.On macroscopic scale the effects of ions on protein-nucleic acid complex extensively studied. B.The microscopic influence of salt on the complex could suggest guidelines for rational design of inhibitors. Fig2:Hermann et al. The picture shows the conserved RNA binding domains RNP1 and RNP2. Cylinders depict a-helices and arrows depict b-strands.

Method: Molecular Dynamics simulations AMBER & SHAKE were used. Results: Fig4:Hermann et al., Stereo view of high occupancy sites for Na+(blue). B-strands as arrows, a-helices as cylinders, RNA(coloured orange). Calculated by integration of the spatial distribution of ions over the MD trajectories. Fig3:Hermann et al., Density distributions of ions around the solute RNA(left) and protein(right), calculated for the starting configuration(top) and after 1.5ns(bottom).

Fig5:Hermann et al.- R.M.S. deviations of the structures of RNA(orange-red) and protein(black,blue) at 0.1M(left) and 1M(right) NaCl. Fig6:Hermann et al.- Differences between the per-residue B-factors of U1A in the MD simulations at 1.0M and 0.1M NaCl.

Fig7:Hermann et al. - a.Deviation of residues from the crystal structure at 0.1M(left) and 1.0M(right) NaCl concentrations where low deviation(blue) and high deviation(red and purple) are shown.

Are the previous results reliable? Contradiction before:”dynamics of residues within the RNP motif are not affected by the salt concentration while outside the conserved regions strong dependence of residue flexibility on ionic strength is observed.” now:” the RNA-binding region that is destabilized by salt and the region that contains helix aA which is stabilized.” Fig8:Hermann et al. - Figure shows the distances between the heavy atoms of the hydrogen donor and acceptor groups.On the left the NaCl is at 0.1M and on the right 1.0M.

The authors conclusions on the experimental data: A.The increased dynamics of the intermolecular bonds at the examined interface observed in the simulations are the basis for the salt induced dissociation of the complex. B.Simulations of 1ns have been sufficient to reveal the stabilizing influence of salt on the structure of a peptide. C.Destabilization may represent the reverse of the association process. Conclusions on the article: a.the RNA is destabilized as all data agree b.the hydrogen bonds between RNA and U1A also destabilized, although “due to the short simulation time it cannot be ruled out that disrupted contacts may be re-established “-results not very useful. c.the effects of the increased salt concentration on the protein seem to contradict and although it is unclear as to whether the salt destabilizes or leaves unaffected the RNA-binding domains, the effect of the salt on the rest of the protein varies by stabilizing, destabilizing or leaving unaffected the residues-results not very convincing. d.the effects of the increased ionic strength on the protein need to be studied further on the microscopic scale.